Project Details
Early Career
Status: Funded - Closed
Extending therapeutic efficacy studies to improve surveillance for drug- and diagnostic-resistant malaria in Ethiopia
Summary
BACKGROUND: Diagnosis and treatment are key components of malaria control; however, the Ethiopia National Malaria Control Program (NMCP)have limited advanced laboratory infrastructure required to conduct molecular surveillance for markers of key antimalarial drug and diagnostic resistance mutations. Molecular determination of drug resistance and pfhrp2/3 deletion prevalence performed in this study will provide key inputs for the NMCP in Ethiopia and the global malaria community. GAP: Incomplete understanding of the true prevalence of antimalarial drug resistance and pfhrp2/3 deletions are knowledge gaps required by the NMCP to make informed policy decisions. HYPOTHESIS: The study hypothesizes low prevalence of antimalarial drug resistance markers and high prevalence of pfhrp2/3 deletions in the study sites, based on our prior work and surveillance data from neighboring countries METHODS: Extracted DNA will be used for multiplex amplicon deep sequencing, targeting known markers of antimalarial drug resistance; and pfhrp2/3 deletion genotyping using a multiplex real-time PCR assay. RESULTS: A total of 420 (2019-21) recent and 275 (2008-15) samples were analyzed in this study. The study has the following major findings. 1. The data confirmed the recent alarming emergence and spread of pfhrp2/3 deletion in the study area and supports the current recommendation of changing the pfhrp2/3 based rapid diagnostic methods by the national malaria control and elimination program of Ethiopia 2. The preliminary data analysis revealed varying frequency of different drug resistance markers. Among the studied drug resistance markers CRT and MDR mutation were found to be fixed. But most importantly two ACT resistance markers were identified: the presence of an ACT resistance (622I) recently reported by our own group is confirmed, in addition a new ACT resistance marker that has never been reported in Ethiopia (568V), was detected. This finding is under validation with another method. This finding is unique both for identifying the markers for the first time in Ethiopia and the markers were found from clinical samples that showed the potential challenge of the only arsenal in the treatment the deadly parasite P. falciparum. IMPACT: The study outcome will be used by the NCMP to further determine antimalarial drug and malaria diagnostic testing policy, so as supporting the fight against malaria that is disproportionately affecting children and pregnant women.
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